Senescent changes in human vision have been well documented, but the factors responsible for these changes are only partially understood. The proposed research is intended to provide fundamental data on aging of the human visual system using methods that separate the relative contributions of optical and neural mechanisms. This research builds on a program demonstrating that age-related losses in the visual pathways have a profound effect on early stage processing but are compensated to a surprising degree to maintain constancy of perception. The overarching theme of the proposed research is to understand temporal dynamics of adaptation, compensation and neuroplasticity at several time scales and levels of processing. Aim 1 compares normal aging and early-stage age-related macular degeneration. Temporal dynamics and retinal adaptation mechanisms will be studied under scotopic and photopic conditions using the full-field and multifocal ERG. Response interactions will be analyzed to understand functional sites of aging and adaptation in the outer retina. These functional data will be correlated with sequenced opsin genes and complement factor H alleles, and with ultra-high resolution images to study photoreceptor numbers and outer retinal morphology, including relations with drusen. Aim 2 will explore temporal dynamics and gain mechanisms under conditions that are dominated by the response of magno-, parvo- or konio-cellular pathways. The hypothesis to be tested is that the OFF subdivisions of these pathways are affected more in senescence than are the ON subdivisions. This will be evaluated by measuring a psychophysical impulse response function and by a psychophysical probe to quantify age-related changes in gain control mechanisms of magno- and parvo-cellular pathways. Aim 3 is concerned with putative cortical compensation mechanisms. While most methods define the adaptation midpoint, the first experiment for this aim is concerned with how adaptation adjusts the range or variance of color signals along cardinal and higher-order color axes. A second study will measure adaptation to higher- order ocular aberrations using a custom adaptive optics phoropter. Finally, patients with diabetic retinopathy will be tested following retinal photocoagulation therapy to determine whether some losses in vision are compensated by expansion of areas subserving spatial summation, similarly to enlargements of spatial summation areas associated with age-related losses in photoreceptors and ganglion cells. These experiments are guided by current hypotheses about the manner in which visual performance may be affected by normal senescence and by age-related macular degeneration and diabetic retinopathy. In addition to providing basic data on the aging visual system, the experiments will provide probes for models of how the visual system adapts and compensates for degradations in the optical and neural images that occur with senescence and disease. PUBLIC HEALTH RELEVANCE: The purpose of this research is to understand the optical and neural foundations of age-related changes in the human visual system. Behavioral and electrophysiological methods are used to probe sites of adaptation and neuroplasticity in the retina and higher-level visual pathways.